A Long-Term Energy-Rich Diet Increases Prefrontal BDNF in Sprague-Dawley Rats

Findings of the effect of high-fat feeding including “Cafeteria Diets” (CAF) on brain-derived neurotrophic factor (BDNF) in the hippocampus (HIP) and prefrontal cortex (PFC) in rodents are conflicting. CAF is a non-standardized, highly palatable energy-rich diet composed by everyday food items for human consumption and is known to induce metabolic syndrome and obesity in rats. However, the highly palatable nature of CAF may counteract a negative effect of chronic stress on anticipatory behavior and synaptic plasticity in the hippocampus, hence represent a confounding factor (e.g., when evaluating functional effects on the brain). This study investigated the effects of a chronic, restricted access to CAF on BDNF, monoamine neurotransmitters, and redox imbalance in HIP and PFC in male rats. Our results show that CAF induced BDNF and its receptor TrkB in PFC compared to the controls (p < 0.0005). No differences in monoamine neurotransmitters were detected in either PFC or HIP. CAF increased dehydroascorbic acid and decreased malondialdehyde in PFC (p < 0.05), suggesting an early redox imbalance insufficient to induce lipid peroxidation. This study supports that a chronic CAF on a restricted schedule increases BDNF levels in the PFC of rats, highlighting that this may be a suboptimal feeding regime when investigating the effects of diet-induced obesity in the brain and emphasizing this as a point of attention when comparing the findings.

Senescence-Mediated Redox Imbalance in Liver and Kidney: Antioxidant Rejuvenating Potential of Green Tea Extract

This study investigates the catechin composition and protective effect of green tea extract on senescence-mediated redox imbalance in the livers and kidneys of aged mice. The results showed that the seven catechins in the green tea extract analyzed in this study could be completely separated within 30 min and the main components of catechins in green tea extract were EGCG, EGC and ECG. In terms of the anti-senescence effects of green tea extract, green tea extract supplementation at doses of 125, 625 and 1250 mg/kg for 4 weeks significantly alleviated the senescence-mediated redox imbalance, as exhibited from significantly (p < 0.05) reduced thiobarbituric acid-reactive substances (TBARS) and protein carbonyls levels in the serum, and increased glutathione (GSH) and total thiols contents in the plasma. Additionally, hepatic and renal protein carbonyls levels were significantly diminished (p < 0.05) and the activities of superoxide dismutase (SOD), catalase, glucose-6-phosphate dehydrogenase (G6PD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd) in the liver and kidney were remarkably elevated (p < 0.05). Overall, these results clearly show that green tea extract exhibits extremely potent protective effects against senescence-mediated redox imbalance in the livers and kidneys of mice by inhibiting oxidative damage of lipids and proteins and increasing the activities of antioxidant enzymes in organs.

Azima tetracantha Leaf Methanol Extract Inhibits Gastric Cancer Cell Proliferation through Induction of Redox Imbalance and Cytochrome C Release

Azima tetracantha is a traditionally used medicinal plant in the Ayurvedic system and folk medicines. The plant has been used for various purposes including inflammatory ailments, arthritis, and various types of toxicities. There are no available reports on its anticancer activity; hence, the study aimed to evaluate its anti-proliferative potential in gastric cancer cells (AGS and KATO III). We observed a dose-dependent decrease in cell proliferation in both the gastric cancer cells; furthermore, a concomitant reduction in the cellular antioxidant status was observed. Pre-treatment with A. tetracantha methanol extract showed a significant reduction in intracellular glutathione levels, and subsequently raised thiobarbituric acid reactive substances. Together with this, a significant increase in the cytochrome c release was noted in A. tetracantha treated cells, alongwith an increase in the expression of pro-apoptotic genes such as BAX, CASP3, CASP7 and APAF1. Furthermore, RTqPCR analysis indicated an increased expression of the anti-apoptotic gene BCL2 in a dose-dependent manner. In addition, to confirm the role of reactive oxygen species in the proliferation inhibition, DCFH-DA-based analysis was carried out, where a dose-dependent increase in ROS levels was observed in these cells. Overall, the study confirms the anticancer efficacy of A. tetracantha leaf methanol extract mediated through the induction of redox imbalance and cytochrome c release.

Salivary gland dysfunction and salivary redox imbalance in patients with Alzheimer’s disease

Alzheimer’s disease (AD) is associated with the deposition of β-amyloid in the brain. AD accounts for over 50% of cases of dementia which results from disturbances in redox homeostasis. Indeed, increased intensity of protein oxidation and nitration as well as lipid peroxidation is observed in brain areas with considerable amounts of amyloid plaques and neurofibrillary tangles. However, little is known about the oxidoreductive balance of salivary glands in AD patients. Therefore, the aim of this study was to evaluate the antioxidant barrier and oxidative/nitrosative stress biomarkers in stimulated saliva and blood of AD patients. The study was participated by 25 AD patients and 25 non-demented controls without neurological diseases or cognitive impairment, matched by age and gender to the study group. The number of patients was determined based on a previous pilot study (test power = 0.9). We found a significant decrease in the activity of erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx), increased activity of catalase (CAT) and reduced concentration of plasma non-enzymatic antioxidants (uric acid, UA and reduced glutathione, GSH). In contrast, in the stimulated saliva of AD patients we observed significantly decreased activity of all antioxidant enzymes (SOD, CAT and GPx) as well as concentration of GSH compared to the control group. The content of lipid (malondialdehyde, MDA) and protein (advanced oxidation protein products, AOPP; advanced glycation end-products, AGE) oxidation products as well as biomarkers of nitrosative stress (peroxynitrite, nitrotyrosine) was significantly higher in both saliva and plasma of AD patients compared to the controls. In AD patients, we also observed a considerable decrease in stimulated saliva secretion and salivary total protein content, and an increase in salivary β-amyloid concentration. In conclusion, AD results in redox imbalance towards oxidative reactions, both at the level of the oral cavity and the entire body. General redox balance disturbances do not coincide with salivary redox balance disturbances. Reduction in stimulated saliva secretion in AD patients reflects secretory dysfunction of the parotid glands.

The impact of sleep apnea syndrome on the altered lipid metabolism and the redox balance

Background Obstructive sleep apnea (OSA) is a disorder with a significant risk for cardiovascular diseases. Dyslipidemia and redox imbalance belong to potential mechanisms linking OSA with the development of vascular diseases. The main aim of this study was the evaluation of the presence of lipid abnormalities in OSA patients, focusing on small dense low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions and determination of the redox imbalance by evaluating the marker of oxidative damage to plasma lipids - lipoperoxides. Methods The study included 15 male subjects with polysomnographically confirmed OSA and 16 male healthy controls. Plasma levels of total cholesterol, LDL and HDL and their subfractions, triacylglycerols and lipoperoxides were determined in all study individuals. Plasma LDL and HDL subfractions were separated by the Lipoprint system which is a polyacrylamide gel electrophoresis. Lipoperoxide levels were determined spectrophotometrically. Results OSA patients had significantly higher triacylglycerols, total cholesterol and LDL-cholesterol compared to healthy controls. HDL cholesterol was not significantly different. Of the LDL and HDL subfractions, OSA patients had significantly lower levels of atheroprotective LDL1 and large HDL subfractions and significantly higher levels of atherogenic small dense LDL3–7 and HDL8–10 subfractions. Lipoperoxide levels in patients with OSA were significantly elevated compared to healthy individuals. Conclusion The lipoprotein pro-atherogenic phenotype was found in individuals with OSA characterized by increased levels of atherogenic lipoprotein subfractions and reduced levels of atheroprotective subfractions. In addition, a plasma redox imbalance was found in patients with OSA compared to controls by detecting higher oxidative damage to lipids. Abnormalities in lipoprotein levels in patients with OSA, as well as the redox imbalance, could lead to an acceleration of the atherosclerotic process in predisposed individuals and thus represent a significant risk factor for vasular diseases.

A Combined Spectroscopic and In Silico Approach to Evaluate the Interaction of Human Frataxin with Mitochondrial Superoxide Dismutase

Frataxin (FXN) is a highly conserved mitochondrial protein whose deficiency causes Friedreich’s ataxia, a neurodegenerative disease. The precise physiological function of FXN is still unclear; however, there is experimental evidence that the protein is involved in biosynthetic iron–sulfur cluster machinery, redox imbalance, and iron homeostasis. FXN is synthesized in the cytosol and imported into the mitochondria, where it is proteolytically cleaved to the mature form. Its involvement in the redox imbalance suggests that FXN could interact with mitochondrial superoxide dismutase (SOD2), a key enzyme in antioxidant cellular defense. In this work, we use site-directed spin labelling coupled to electron paramagnetic resonance spectroscopy (SDSL-EPR) and fluorescence quenching experiments to investigate the interaction between human FXN and SOD2 in vitro. Spectroscopic data are combined with rigid body protein–protein docking to assess the potential structure of the FXN-SOD2 complex, which leaves the metal binding region of FXN accessible to the solvent. We provide evidence that human FXN interacts with human SOD2 in vitro and that the complex is in fast exchange. This interaction could be relevant during the assembly of iron-sulfur (FeS) clusters and/or their incorporation in proteins when FeS clusters are potentially susceptible to attacks by reactive oxygen species.

Biomarkers of Inflammation and Redox Imbalance in Umbilical Cord in Pregnancies with and without Preeclampsia and Consequent Perinatal Outcomes

Objective. To compare redox imbalance and inflammation biomarkers in umbilical cords from pregnancies with and without preeclampsia (PE) and to analyse their relationships with perinatal outcomes. Methods. A controlled cross-sectional study was conducted in Maceió, Alagoas, Brazil, that involved pregnant women with PE and a group of women without the disease, through the application of a standardized questionnaire. After delivery, umbilical cord samples were collected to measure antioxidant defense, products from oxidative damage, and inflammation biomarkers such as myeloperoxidase (MPO), interleukin- (IL-) 6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α). Statistical analyses were performed using Stata version 13.0 software and IBM Statistical Package for the Social Sciences (SPSS) 20.0, adopting a 95% confidence level ( α = 0.05 ), with the chi-square test, the Wilcoxon–Mann–Whitney test, and the multinomial and Poisson regression tests. Results. One hundred PE pregnant women and 50 women without the disease were studied. The umbilical cords from PE pregnancies showed higher levels of reduced glutathione (GSH) ( p ≤ 0.001 ), glutathione peroxidase (GPx) ( p = 0.016 ), and malondialdehyde (MDA) ( p = 0.028 ) and lower levels of IL-6 ( p = 0.030 ) and TNF-α ( p ≤ 0.001 ) than the other group, with some associations among these biomarkers with perinatal outcomes. Conclusion. The higher levels of GSH and GPx, in addition to the lower levels of IL-6 and TNF-α, found in the PE umbilical cord, may result from adaptive mechanisms to maintain the oxidative and inflammatory balance; however, despite these changes, the damage to the cell membranes was not minimized, as the MDA level was higher in women with PE than in women without the disease. This implies that a redox imbalance is present, confirming that other physiological and adaptive mechanisms are being activated to preserve foetal health. Therefore, the present work unveils an important role of the umbilical cord in controlling redox imbalance and inflammation in PE pregnancies. Our results reinforce the necessity for continuous research on GSH as a protective compound for the perinatal outcome, especially in PE women.